DESCRIPTION: Rational and Aims: Although mechanisms have not been confirmed, animal and epidemiological studies suggest that antidepressants promote tumor growth in humans. Recently, a study in animals showed that tricyclic antidepressants (TCAs) with a nitrogen atom at position 5 in the 7-membered ring of their chemical structure (5-N) were genotoxic, as compared to those with a carbon atom at the same position (5-C) (Van Schaik et al. Mutation Research 1993, 286(2): 155-163). These results were confirmed in humans by a large epidemiologic study (Sharpe et al. submitted to the British Journal of Cancer, 2000). In this historical population-based case-control study we will investigate the effect of past exposure to 5-N TCAs on the risk of developing cancer at 19 different sites. Methods: The source population for the study will be the dynamic cohort defined by membership in the Saskatchewan Prescription Drug Plan (SPDP). Incident cancer cases (at one of the 19 sites considered) over 5 years of age will be accrued by the provincial cancer registry from 1981 to 1999. At least 4 controls/case will be selected from the source population, matched on age, gender, and calendar time, using incidence density sampling. Detailed drug exposure data over a minimum of 5 years before diagnosis and up to a maximum of 23 years will be obtained from the SPDP. We will study for each drug and each site the respective effects of dosage, timing of use, and duration of use. Significance: If the results show that long-term use of antidepressants affect the incidence of cancer, they will be relevant to clinicians (with an elaboration on the risk/benefit profile of this therapy) and to the pharmaceutical industry (with a view to modifying the structure of drugs to enhance their beneficial effects and to reduce their harmful effects).